Erythropoietin and Endothelial Progenitor Cell Therapy after Myocardial Infarction
Pp. 205-231 (27)
Kamellia R. Dimitrova, Gabriela R. Dincheva and I. Michael Leitman
It is commonly believed that mammalian cardiomyocytes withdraw from the
cell cycle shortly after birth, and postnatal growth of the heart is by hypertrophy rather
than by hyperplasia. Although proliferating myocytes have been detected in the heart in
ischemia and acute myocardial infarction, recent experimental evidence strongly
suggests that these cells derive from circulating and locally released precursor cells.
These discoveries in conjunction with increased incidence and prevalence of heart
disease and few new classes of pharmacologic agents for cardiovascular disease have
paved the way for numerous clinical trials of stem and progenitor cell therapy for acute
myocardial infarction and congestive heart failure. Nearly all trials have demonstrated
safety and feasibility of stem cell therapies for cardiovascular disease. Many have
suggested that the survival of the transplanted cells is improved when applied with
erythropoietin (EPO), resulting in improved clinical outcomes. Besides its
hematopoietic effects erythropoietin has anti-apoptotic effects especially under ischemic
conditions and attenuates oxidative stress. EPO receptors are expressed on erythroid
precursors, megakaryocytes, vascular smooth muscle cells, endothelial cells, skeletal
myoblasts, neurons, nephrons, and cardiac myocytes. Augmentation of this self-repair
process through application of EPO and transplantation of exogenous endothelial
progenitor cells is coming closer and closer to clinical reality. Clinicians will need to
understand the fundamental concepts underlying the preclinical and clinical applications
of EPO and EPCs. This chapter provides a primer on those basic principles.
Erythropoietin, endothelial progenitor cells, stem cell therapy, heart
failure, myocardial infarction.
Division of Cardiac Surgery, Beth Israel Medical Center, New York, NY, USA.